The FIDELIO-DKD Trial in Chronic Kidney Disease

George L. Bakris, MD, describes the design and results of the FIDELIO-DKD trial investigating the effect of finerenone on patients with chronic kidney disease.

Neil B. Minkoff, MD: Dr Bakris, I understand that you were an instrumental part of the paper called FIDELIO-DKD. Could you enlighten us a little on this?

George L. Bakris, MD: Yes, I was a principal investigator, but Dr Agarwal was a key part of the executive committee designing this trial. We’re both to blame, or to be congratulated.

Neil B. Minkoff, MD: I’ll congratulate you.

George L. Bakris, MD: Thank you. When we were designing this trial, we didn’t want to have another typical trial looking at patients with very high-risk kidney disease. We wanted to develop something that would look at the broader scope of albuminuria and kidney disease in the context of cardiovascular risk as well. So we designed 2 trials: FIDELIO and FIGARO-DKD. FIGARO is the cardiovascular component, and it just got published. They were supposed to be a marriage of the 2 studies looking at a much broader spectrum of kidney disease: cardiovascular risk and kidney disease.

FIDELIO was designed to not look like a typical trial. We wanted maximal ACE [angiotensin-converting enzyme] or ARB [angiotensin receptor blocker] background therapy, not just, “Are you on an ACE or an ARB?” So we ensured that was the case. We screened almost 14,000 people to get 5700-plus patients who could tolerate a maximal dose ACE or ARB. Unlike any other trial that’s been published, you can’t really compare the results of this trial to those trials for that reason alone, because most patients weren’t on maximal doses of ACEs or ARBs.

Neil B. Minkoff, MD: Right.

George L. Bakris, MD: What we then did is randomize based on a phase 2 study that we published in JAMA [Journal of the American Medical Association] in 2015 on the doses in which we saw the most reduction in albuminuria, 10 and 20 mg, and compared it with placebo. Then we were vigilant about the potassium. We knew from data we had published much earlier that if your potassium was 4.8 mEq/L and you were already being treated with diuretics, that your risk for hyperkalemia was going to be high. We didn’t want truckloads of people dropping out, and we knew that the hyperkalemia risk wasn’t going to be as great as the other studies, so we limited it to 4.8 mEq/L to be included in the trial. However, people got into the trial with potassium of 5 mEq/L because we measured it again when they came in, and if it was 5 mEq/L, you’re in. That’s why the label from the FDA says you can use it up to a potassium of 5 mEq/L. That’s important.

Long story short, the trial was done and it showed significant slowing of CKD [chronic kidney disease] progression and a significant reduction in cardiovascular risk, driven primarily by heart failure reduction. Now, you could say [finerenone is] a brother to spironolactone. Au contraire! Not a brother, or even a first cousin, but maybe a second cousin. The FDA has given a specific label that this is a new class of agents. Yes, they’re mineralocorticoid receptor antagonists, but the chemistry differs. As Rajiv alluded to, the pharmacology is totally different from the steroidal molecules. As a result, they’re different. This drug barely lowers blood pressure. You get about a 3-mm reduction in blood pressure. With spironolactone, you’re going to get 12-mm reductions in blood pressure. It’s a very powerful antihypertensive.

The take-home message of not only this trial, but if you put together FIGARO and do the analysis that we did, and Rajiv guided the FIDELITY study, which is soon to be published, it makes a very strong point for kidney protection on top of the maximal doses of ACEs or ARBs and significant reduction in heart failure risk and cardiovascular risk, with significant reductions in albuminuria and improvement in kidney function. As you’ll hear in a second, the other drugs in the class are not quite the same, so this is big. In fact, Rajiv, it’s on the shelves because I’ve already written 2 prescriptions for it. It’s out there. That’s my 2 cents.

Transcript edited for clarity.

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